# Chemical Adjustment of Fibrinolysis

**Authors:** Alexey M. Shibeko, Ivan S. Ilin, Nadezhda A. Podoplelova, Vladimir B. Sulimov, Mikhail A. Panteleev

PMC · DOI: 10.3390/ph17010092 · 2024-01-10

## TL;DR

This paper discusses how small chemical compounds can adjust the body's clot-dissolving process, which is important for treating conditions like stroke and fibrosis.

## Contribution

The paper introduces new insights into low molecular weight compounds for regulating fibrinolysis and highlights computational models for drug development.

## Key findings

- Low molecular weight compounds can modulate fibrinolysis without affecting other hemostasis components.
- These compounds may be useful beyond hematology, such as in treating fibrosis.
- Computational models are promising tools for developing new fibrinolysis-targeting drugs.

## Abstract

Fibrinolysis is the process of the fibrin–platelet clot dissolution initiated after bleeding has been stopped. It is regulated by a cascade of proteolytic enzymes with plasmin at its core. In pathological cases, the balance of normal clot formation and dissolution is replaced by a too rapid lysis, leading to bleeding, or an insufficient one, leading to an increased thrombotic risk. The only approved therapy for emergency thrombus lysis in ischemic stroke is recombinant tissue plasminogen activator, though streptokinase or urokinase-type plasminogen activators could be used for other conditions. Low molecular weight compounds are of great interest for long-term correction of fibrinolysis dysfunctions. Their areas of application might go beyond the hematology field because the regulation of fibrinolysis could be important in many conditions, such as fibrosis. They enhance or weaken fibrinolysis without significant effects on other components of hemostasis. Here we will describe and discuss the main classes of these substances and their mechanisms of action. We will also explore avenues of research for the development of new drugs, with a focus on the use of computational models in this field.

## Linked entities

- **Proteins:** plg (plasminogen)
- **Diseases:** ischemic stroke (MONDO:1060198)

## Full-text entities

- **Genes:** F13A1 (coagulation factor XIII A chain) [NCBI Gene 2162] {aka F13A}, PLG (plasminogen) [NCBI Gene 5340] {aka HAE4}, SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, A2M (alpha-2-macroglobulin) [NCBI Gene 2] {aka A2MD, CPAMD5, FWP007, S863-7}, Serpine1 (serine (or cysteine) peptidase inhibitor, clade E, member 1) [NCBI Gene 18787] {aka PAI-1, PAI1, Planh1}, Plg (plasminogen) [NCBI Gene 18815] {aka Pg}, PLAU (plasminogen activator, urokinase) [NCBI Gene 5328] {aka ATF, BDPLT5, QPD, UPA, URK, u-PA}, Plau (plasminogen activator, urokinase) [NCBI Gene 18792] {aka u-PA, uPA}, CPB2 (carboxypeptidase B2) [NCBI Gene 1361] {aka CPU, PCPB, TAFI}, PRH1 (proline rich protein HaeIII subfamily 1) [NCBI Gene 5554] {aka Db-s, PA, PIF-S, PRP-1/PRP-2, Pr1/Pr2}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, SERPINF2 (serpin family F member 2) [NCBI Gene 5345] {aka A2AP, AAP, ALPHA-2-PI, API, PLI, alpha2AP}, THBD (thrombomodulin) [NCBI Gene 7056] {aka AHUS6, BDCA-3, BDCA3, CD141, THPH12, THRM}, PLAT (plasminogen activator, tissue type) [NCBI Gene 5327] {aka T-PA, TPA}
- **Diseases:** Thromboses (MESH:D013927), multiple organ failure (MESH:D009102), seizures (MESH:D012640), spinal cord axonal degeneration (MESH:D013118), coronary artery stenosis (MESH:D023921), insulin resistance (MESH:D007333), demyelination (MESH:D003711), diabetic (MESH:D003920), DIC (MESH:D004211), liver fibrosis (MESH:D008103), breast cancer (MESH:D001943), hemophilia (MESH:D006467), Sepsis (MESH:D018805), allergic encephalomyelitis (MESH:D004681), coagulation impairment (MESH:D025861), intracranial bleeding (MESH:D013345), vascular damage (MESH:D057772), COVID-19 (MESH:D000086382), albuminuria (MESH:D000419), ischemic stroke (MESH:D002544), postoperative bleeding (MESH:D019106), fibrosis (MESH:D005355), ICH (MESH:D002543), injury to people or property (MESH:C000719191), metabolic syndrome (MESH:D024821), Bleeding (MESH:D006470), hypoxia (MESH:D000860), deficiency (MESH:D007153), middle cerebral artery occlusion (MESH:D020244), weight gain (MESH:D015430), traumatic brain injury (MESH:D000070642), heart attacks (MESH:D009203), deep vein thrombosis (MESH:D020246), trauma (MESH:D014947), Blood coagulation (MESH:D001778), ischemic cardiovascular disease (MESH:D002318), hypertensive (MESH:D006973), venous thromboembolism (MESH:D054556), ischemia (MESH:D007511), strokes (MESH:D020521), platelet function (MESH:D001791), paralysis (MESH:D010243), postoperative renal dysfunction (MESH:D007674), infarction (MESH:D007238), fibrinolysis dysfunctions (MESH:D006331)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10819531/full.md

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Source: https://tomesphere.com/paper/PMC10819531